Abstract 4522: Hypoxia-induced alteration of mitochondrial dynamics is linked to chemoresistance in ovarian cancer

Abstract

Abstract Hypoxia, commonly observed in the tumor microenvironment, has been shown to be related to the cancer hallmarks. Hypoxia generates reactive oxygen species (ROS), inducing changes in mitochondrial function and structure in various diseases. Mitochondria, dynamic intracellular organelles, go through incessant processes of fission and fusion for efficient generation of energy. We investigated alterations in mitochondrial networks under hypoxic conditions (< 1 % O2) and subsequent effects of the mitochondrial alteration on drug response in ovarian cancer cells. Mitochondrial fission was prevalent in cancer cells under hypoxic conditions. Translocation of phospho-Drp1 (Ser616), a biochemically active mitochondrial fission protein, to mitochondria was enhanced under hypoxic conditions. An increase in ROS production was accompanied under hypoxic conditions. ROS scavenging reversed the hypoxia-elicited mitochondrial fission, while exogenous H2O2 treatment promoted mitochondrial fission. These results strongly implicate that ROS are important modulators of mitochondrial dynamics under hypoxia. Interestingly, hypoxia-induced mitochondrial fission altered the response of cancer cells to cisplatin (CDDP). Ovarian cancer cells in hypoxic and normoxic conditions were differentially affected by CDDP when mitochondrial fission was inhibited. Taken together, the alteration of mitochondrial dynamics, a cellular adaptation to hypoxia, is associated with chemoresistance. Mitochondria adapted to the hypoxic tumor microenvironment could be a potential target for anti-cancer therapy. Citation Format: Youngjin Han, Boyun Kim, Yong Sang Song. Hypoxia-induced alteration of mitochondrial dynamics is linked to chemoresistance in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4522. doi:10.1158/1538-7445.AM2017-4522